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COL17A1 (collagen type XVII alpha 1 chain) is known to be upregulated and has a prognostic role in many malignancies, as well as contributing to cell proliferation, apoptosis, and invasion. However, little knowledge is available on the expression and prognostic value of COL17A1 in pancreatic adenocarcinoma (PDAC). In our study, we searched the public database and found that mRNA and protein levels of COL17A1 are commonly upregulated in PDAC tissues. The immunohistochemical analysis conducted by us revealed enhanced expression of COL17A1 protein in 169 PDAC samples compared with that in 67 adjacent normal tissues. We also observed a significantly positive correlation between COL17A1 expression and lymph node metastasis ( p < 0.0001 ), TNM clinical stage ( p < 0.0001 ), and pathology differentiation ( p < 0.01 ). The KM-plot results indicated that PDAC patients with a high COL17A1 expression have a poorer overall survival ( p < 0.001 ) than those with a low COL17A1 expression. The result of the Cox regression analysis of multivariate data suggested COL17A1 is an independent prognostic indicator of PDAC patients’ overall survival. CCK-8, wound healing, and transwell assays suggested that COL17A1 knockdown markedly inhibited tumor proliferation and invasion in PDAC cells, and cells with COL17A1 overexpression had a prominently higher proliferative and invasive capacity. Knockdown of COL17A1 significantly upregulated the apoptosis rate. We deduce that upregulated COL17A1 activated the NF-κB pathway in PDAC cells. In summary, our studies showed the prognostic value of COL17A1 in PDAC and that COL17A1 may act as a molecular therapeutic target for PDAC treatment.

We sought to compare the prevalence and volume of lipid plaque, fibrous plaque, and calcified plaque in patients with smokers versus nonsmokers.We studied consecutive patients suspected of coronary artery disease and who underwent coronary computed tomography angiography. A structured interview and review of existing clinical data was conducted before computed tomography angiography to collect information on demographic characteristics, the presence of cardiovascular risk factors. The volume of lipid, fibrous, and calcified plaque were automatically calculated and marked in different colors according to predefined Hounsfield unit thresholds. The prevalence and volume of plaques were compared between smokers and nonsmokers.Overall 6380 patients (3351 men and 3029 women, mean age 55.35 years) were finally analyzed, of whom 2075 (32.5%) were smokers, and 4305 (67.5%) were never smokers. The prevalence of any plaque in smokers was significantly higher compared to never smokers (47.7% vs. 32.3%, p0.001). Smoking was an independent risk factor of the presence of any plaque after correcting for age, gender, body mass index, hypertension, dyslipidemia, diabetes, and family history in a multivariate model (odds ratio = 1.250 (1.088-1.437), p = 0.002). The volume of lipid plaque, fibrous plaque, calcified plaque, and total plaque in smokers was significantly greater than nonsmokers (p0.001).The prevalence and volume of lipid plaque, fibrous plaque, and calcified plaque were significantly higher in smokers versus never smokers.

Identifying disease activity in Takayasu arteritis (TAK) is challenging. This study aimed to investigate the value of quantitative characterization with computed tomography angiography in the assessment of disease activity in patients with TAK.We retrospectively analysed the data on 162 aortic CT angiography from 140 TAK patients. Patients were categorized based on disease activity according to the National Institutes of Health criteria into two groups: active disease group (n = 65) and inactive disease group (n = 97).Patients with active TAK had a thicker wall compared with patients with inactive TAK (5.2 ± 2.4 mm vs. 2.5 ± 0.8 mm, p 0.001). The relative post-contrast enhancement ratio of the thickened wall was higher in active TAK than in inactive TAK (1.5 ± 0.3 vs. 1.1 ± 0.2, p 0.001). Given a thickness cutoff of 3.3 mm, sensitivity for active-phase TAK was 83.1%, specificity 89.7%, positive predictive value 84.4%, and negative predictive value 88.8%. With a relative post-contrast enhancement ratio cutoff of 1.2, sensitivity for active-phase TAK was 89.2%, specificity 76.3%, positive predictive value 71.6%, and negative predictive value 91.3%. In receiver-operating characteristic curves comparison, maximal wall thickness and relative post-contrast enhancement ratio were superior to C-reactive protein and erythrocyte sedimentation rate for determining active phase disease (p 0.05).Quantitative characterization with CT angiography was a useful tool to assess disease activity in TAK patients. Maximal wall thickness and relative post-contrast enhancement ratio have a high sensitivity and specificity for detecting TAK activity.

To investigate prognostic significance of follow-up CT findings for initially medically treated type B aortic intramural hematoma (IMH). We performed a retrospective pooled analysis of individual patient data, including baseline and follow-up CT characteristics. All enrolled patients were followed up for adverse aorta-related events, defined as a composite of aortic disease–related death and surgical or endovascular aortic repair. A total of 238 patients (73.9% men) were included, with a mean age of 58.1 ± 9.8 years. During follow-up, 83 patients (34.9%) experienced adverse aorta-related events, most of the events (83.1%) occurred within 1 month after follow-up CT imaging (n = 69). In the Cox regression model for predicting adverse aorta-related events, baseline maximal aortic diameter (MAD) (HR = 1.05, p = 0.008), ulcer-like projection (ULP) (HR = 2.47, p

BACKGROUND Ambulatory cancer patients carry a high risk of venous thromboembolism (VTE). However, the optimal prophylaxis strategy remains controversial. This meta-analysis compared the effectiveness and safety of apixaban, rivaroxaban, low molecular weight heparin (LMWH), semuloparin, aspirin, and warfarin for the prevention of VTE in ambulatory cancer patients. METHODS A systematic review and network meta-analysis was performed. PubMed, the Cochrane Central Register of Controlled Trails (CENTRAL) and EMBASE electronic databases were searched from inception to 26 April 2019. In the meta-analysis, 19 randomized controlled trials (RCTs) in ambulatory cancer patients administrated venous thromboprophylaxis agents were included. The primary outcome was the risk of VTE. Safety outcomes included the occurrence of major-bleeding. Two investigators identified the studies and performed data extraction. A network meta-analysis was performed and agents were ranked using cumulative ranking (SUCRA) probabilities. RESULTS We identified 19 studies, including 11,430 patients comparing 10 interventions. Compared to placebo controls, apixaban (5 mg) showed the highest efficacy for the prevention of VTE [odds ratio (OR) 0.36, 95% confidence interval (CI): 0.18-0.71, SUCRA=69.5] and was more effective than LMWH (OR 0.5, 0.39-0.63; SUCRA=52.1) or warfarin (OR 0.75, 95% CI: 0.35-1.59; SUCRA=25.6). Moreover, the safety of apixaban (5 mg) (OR 1.41, 95% CI: 0.33-5.93; SUCRA=58.5) was higher than LMWH (OR 1.96, 95% CI: 0.99-3.86; SUCRA=44.1) or warfarin (OR 3.06, 95% CI: 1.03-9.08; SUCRA=29.1). There were no significant differences between placebo and experimental groups in terms of patient deaths. CONCLUSIONS Anticoagulation therapies in ambulatory cancer patients can significantly reduce the risk of VTE. However, this protective effect was associated with a significantly increased risk of major bleeding. Apixaban at the appropriate dose can decrease the risk of VTE without increasing the bleeding risk. These findings require validation in larger study cohorts.

Background Prior studies provided limited data regarding natural history of initially medically treated type A intramural hematoma (IMH). Objectives To develop predictive models for adverse aorta-related events in patients with type A IMH. Methods We performed a retrospective pooled analysis of individual patient data, including baseline clinical and CT characteristics. All patients enrolled were followed up for adverse aorta-related events, defined as a composite of aortic disease-related death and the presence of aortic complications that required aortic invasive treatment. Results A total of 172 patients (52.9% men) were included, with a mean age of 61.1 ± 11.2 years. During a median follow-up time of 770.5 (45.3-1695.8) days, 60 patients (34.9%) experienced adverse aorta-related events. In Cox regression model for predicting adverse aorta-related events, hypertension (HR = 3.78, p = .067), MAD (HR = 1.05, p = .018), presence of ULP (HR = 2.43, p = .002) and pericardial effusion (HR = 1.65, p = .061) were independently associated with adverse aorta-related events. A majority of the adverse aorta-related events (n = 46, 76.7%) occurred within acute and subacute phase (90 days) of IMH. In predictive model for 90 days aortic events, MAD≥50.7 mm (OR = 2.79, p = .006) and presence of ULP (OR = 3.20, p = .002) were independent predictors. C statistic of the predictive model were 0.71 (p Conclusions Predictive models including baseline clinical and CT characteristics as predictors allow for accurate estimation of risk of adverse aorta-related events in patients with type A IMH. The proposed predictive models are helpful for risk estimates and decision making.

There are limited data assessing statin therapy in patients with nonobstructive coronary plaque on coronary computed tomography angiography (CCTA).Two hundred six consecutive patients with mild noncalcified plaque on CCTA were enrolled in this multicenter prospective observational study. Subjects were divided into 3 groups according to subsequent statin therapy: intensive statin therapy (n = 55), moderate statins (n = 85), and no statin (n = 66). Serial scans were performed after a median interval of 18 months. Low-attenuation plaque (LAP) volume, total plaque volume, and percent plaque volume were measured.The LAP volume, total plaque volume, and percent plaque volume showed significant regression among intensive-statin compared with no-statin group (annualized changes: -7.1 ± 13.1 vs 0.9 ± 12.7 mm(3), P.001; -16.4 ± 35.0 vs 12.3 ± 32.4 mm(3), P.001; and -6.2% ± 11.8% vs 3.5% ± 12.1%, P.001, respectively). Progression of LAP volume, total plaque volume, and percent plaque volume was retarded among moderate-statin compared with no-statin group (annualized changes: -2.8 ± 7.6 vs 0.9 ± 12.7 mm(3), P= .041; -0.1 ± 25.6 vs 12.3 ± 32.4 mm(3), P= .014; and -1.8% ± 11.2% vs 3.5% ± 12.1%, P= .006, respectively). On multivariable model predicting change in total plaque volume, higher baseline LAP volume, moderate statin therapy, and intensive statin therapy were each independent predictors of plaque regression (standardized coefficients: baseline LAP volume -0.36, P.001; moderate statin -0.21, P= .004; intensive statin -0.36, P.001, respectively).This study suggests that statin treatment can retard progression and even induce regression of mild noncalcified coronary plaque. Patients with greater baseline LAP volume are more likely to benefit from statin therapy.

Marital status is an independent prognostic factor for survival in several cancers. To determine if that is also true for pancreatic cancer after surgical treatment, we examined 13,370 cases of pancreatic cancer reported to the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2012. We found that patients who were widowed at the time of diagnosis were more likely to be female, a high percentage were elderly, a high ratio were diagnosed in early years, and a high proportion of tumors were located at the head of the pancreas (P < 0.05). Marital status was confirmed to be an independent prognostic factor in both univariate and multivariate analyses (P < 0.05). In those with localized disease, 5-year pancreatic cancer cause-specific survival was 6.5% lower in widowed patients than married ones (38.6% vs. 32.1%), though this difference was not significant in a multivariate analysis (P = 0.084). In those with regional disease or distant metastasis, univariate and multivariate analyses indicated marital status to be an independent prognostic factor (P < 0.05). Thus marital status is an important prognostic factor in pancreatic cancer, and widowed patients are at greater risk of death than others.

Ethnopharmacological relevance Dengue is one of the most important pervasive diseases in many regions of the world, including China. There is an urgent need for new repellents, including plant derivatives, due to the resistance, toxicity, and non-degradability of synthetic insecticides. Traditional plant-based remedies may provide potential avenues for developing new strategies. Aims of the study The aims of this study were to 1) document the traditional mosquitoes repellent plants used by the Dai people of Xishuangbanna, China; 2) screen out new efficient mosquito repellent plants as candidates for further study. Materials and methods During the period August 2016 to July 2017, five field surveys were conducted in 16 villages of Xishuangbanna. A total of 81 informants (44 males and 37 females) were interviewed using semi-structured questions to collect detailed information on the plants they use to prevent mosquito bites. Ten plants with higher popularity and larger resource were collected and extracts were prepared by hydro-distillation or with petroleum ether. Extracts were tested for adult Aedes albopictus repellency using a human-bait cage. Firstly, repellency was determined as the Minimum Effective Dosage (MED) per minute at which 1% of the mosquito bite through the treated cloth. Secondly, five plant extracts with lower MEDs were tested the repellent longevity of different concentrations. Results Eighteen plants were documented as being used in traditional remedies against mosquitoes. The methods for controlling mosquitoes were diverse: direct burning was used for most plants (16 species), followed by smearing (5 species), and placing (5 species). Laboratory analyses confirmed that ten plants did exhibit mosquito repellent activity. Of them, Artemisia indica, Nicotiana tabacum, Blumea balsamifera, Vitex trifolia, and Chromolaena odorata showed good mosquito repellency with MEDs of 0.015, 0.061, 0.090, 0.090, and 0.105 mg/cm2, respectively. The protection rate provided by A. indica is also the highest among five plants. Although it provides complete protection time of only 30 min at 0.45 mg/cm2 concentration, its repellency within 2 h is not significantly different from that of DEET. Conclusion Dai villagers in Xishuangbanna have a rich, diverse and scientific knowledge of plant-based mosquito repellents. Laboratory experiments screened out several plants as candidates for mosquito repellents, of which Artemisia indica was the most promising candidate plant.

Drug resistance is a major problem in the treatment of pancreatic cancer (PC). Long noncoding (lnc)RNAs modulate a variety of cellular processes. This study was carried out to identify lncRNAs that are differentially expressed in drug-resistant PC by next-generation RNA sequencing. We identified 205 differentially expressed lncRNAs (DELs) and 847 differentially expressed mRNAs (DEMs) in a comparison of gemcitabine-resistant and -sensitive SW1990 human PC cells. The expression levels of 12 randomly selected lncRNAs were confirmed by quantitative real-time PCR. A total of 55 and 99 DEMs were predicted to be targeted by the DELs through cis and trans mechanisms, respectively. The DEMs were significantly enriched in the Gene Ontology terms cell part, binding, and cellular processes, and a Kyoto Encyclopedia of Genes and Genomes analysis showed that they were associated with metabolic pathway, pathways in cancer, insulin resistance, microRNAs in cancer, and phosphotidylinositol 3-kinase-Akt signaling pathway. A coexpression network revealed a hub comprising lncRNAs (MIR210HG, SNHG1, and LOC729970) and mRNAs (RAB3D, DDX17, and SPNS2) that presumably mediate drug resistance in PC. The identified lncRNAs can serve as diagnostic or prognostic biomarkers and therapeutic targets for PC.

Author(s): Hou, Zhi-Hui; Lu, Bin; Li, Zhen-Nan; An, Yun-Qiang; Gao, Yang; Yin, Wei-Hua; Budoff, Matthew J

Bicuspid aortic valve (BAV) is a common congenital heart disease. Our study was to analyze clinical features of BAV and evaluate whether aortic valve calcium score (AVCS) was a reliable marker for aortic stenosis (AS) in patients with BAV. 101 patients with BAV who both underwent echocardiology and cardiac computed tomography (CT) scan in our institution were included. Basic clinical data, haemodynamic feature, aortic valve and coronary calcium score were collected and compared among patients with different valve function and different degree of AS. Risk factors related to severe AS were evaluated by logistic regression, and a receiver operative characteristic curve was used to determine the cutoff calcium score greater than which the diagnosis of severe AS was optimized. Patients with aortic regurgitation (AR) were younger and demonstrated larger aortic annulus and sinus compared with patients with other valve dysfunction. Aortic valve calcium score was higher in patients with AS than with AR. For patients with different degree of AS, there were statistical significances in the value of age, aortic valve calcium score and coronary calcium score. AVCS was positively related to severe AS with an odd ratio of 1.286 (95% CI 1.099-1.504) by every 300 points increase. AVCS was also a strong predictor for severe AS with area under the curve 0.855 with a cutoff value of 897 (sensitivity 86.7%, specificity 72.2%). Conclusively, aortic calcium score calculated by quantitative CT is a reliable marker in evaluating severity of AS.

To compare the difference of coronary diameter stenosis by quantitative analysis of CT angiography (QCT) in the systolic (QCT-S) and diastolic phase (QCT-D) of the cardiac cycle, with invasive catheter angiography (QCA) as reference standard.A total of 109 patients (57.5 ± 10.6 years, 78.9% male) with suspected coronary artery disease (CAD) who underwent both CT angiography and invasive catheter angiography were retrospectively included in this study. Coronary diameter stenoses in systolic and diastolic coronary CTA reconstructions were compared with QCA.Mean time interval between CT angiography and invasive angiography was 17.4 ± 4.4 days. QCT-D overestimated coronary diameter stenosis by 5.7%-8.5% while QCT-S overestimated coronary diameter stenosis by 9.4%-11.9% (p 0.05). In calcified lesions, QCT-D overestimated coronary diameter stenosis by 13.2 ± 4.3%, while QCT-S overestimated by stenosis by 16.6 ± 4.3% (p 0.05).Coronary diameter stenosis was overestimated by QCT-D as well as QCT-S, respectively, when compared with QCA. Overestimation was more pronounced in calcified lesions.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which participates in inhibiting tumor apoptosis in pancreatic cancer cells. Using immunohistochemical staining, we investigated the expression of CIP2A protein in 72 cases of human pancreatic ductal adenocarcinoma (PDAC) tissue and 27 cases of adjacent normal pancreatic tissue. The positive rate of CIP2A protein expression in pancreatic cancer tissue was70.83 %, which was significantly higher than that in adjacent non- cancerous pancreatic tissue (11.11%). The expression of CIP2A was found to be correlated with TNM stage, but not correlated with age, gender, tumor location, smoking status, alcohol consumption, diabetes, high blood pressure, BMI, tumor size, lymph node metastasis or distant metastases. Kaplan- Meier survival analysis showed that patients with positive CIP2A protein expression had a lower overall survival rate than patients without CIP2A expression. COX regression analysis indicated that expression of CIP2A was an independent prognostic factor for pancreatic ductal adenocarcinoma. In addition, down-regulation of CIP2A inhibited cell proliferation and increased sensitivity to gemcitabine in pancreatic cancer cells by decreasing AKT signaling pathway. Our results indicated that down-regulation of CIP2A could be a novel therapeutic strategy for pancreatic cancer.

Background Surveys that describe the utilization of cardiac CT are available for the United States, Germany, and Taiwan, but not mainland China. Objectives To analyze the clinical utilization of cardiac CT in mainland China. Methods A 25-item questionnaire was created and 240 tertiary hospitals were randomly selected to participate. Survey data were collected and confirmed by email as well as phone interviews. Results In total, 237 (99%) hospitals consented to this survey, but 85 were excluded because of lack of cardiac CT patient volume or advanced technology. Finally, 152 (64%) questionnaires were available for analysis. Median patient volume was 1,037 patients (range: 150–8,072) annually. The most common clinical indications for coronary CT angiography were exclusion of coronary artery disease in patients with low to intermediate pretest likelihood, asymptomatic individuals with cardiovascular risk factors, and follow-up after coronary bypass grafting. The median heart rate threshold for beta blocker administration was >70 beats/min; most centers (86%) used sublingual nitroglycerin. Prospectively ECG triggered acquisition was the predominant technique in 44% of hospitals. Most (59%) providers adjusted the tube current to the body mass, but few (16%) adjusted the contrast injection rate. Per case, the mean examination duration was 14.2 min; post-processing time 13.6 min; and reporting time 18.0 min. Conclusions Cardiac CT is widely established in clinical practice in mainland China but there is a need for more uniform standards regarding performance and clinical utilization.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly human malignant diseases and the sixth leading cause of cancer-related deaths in China. Gemcitabine is the only first-line chemotherapeutic agent used for the palliative treatment of patients with PDAC, but chemo-resistance limits their efficacy. Here, we showed that miR-125a was up-regulated in chemo-resistant SW1990GZ cells when compared with SW1990 cells. Over-expression of miR-125a increased the chemo-resistance to gemcitabine in SW1990 cells, while down-regulation of miR-125a in SW1990GZ cells increased chemo-sensitivity to gemcitabine. By using bioinformatics analysis tool (Targetscan), the 3' untranslated region (3'UTR) of A20 gene was found to be a target of miR-125a. Luciferase reporter assay further confirmed that A20 3'UTR is a direct target of miR-125a. Over-expression of A20 in SW1990 cells increased chemo-sensitivity to gemcitabine, while knockdown of A20 in SW1990 cells promoted the chemo-resistance to gemcitabine. Finally, the expression level of miR-125a in pancreatic cancer tissues from chemo-sensitive patients was significantly lower than that from chemo-resistant patients, and was inversely correlated with the A20 mRNA levels. In conclusion, our results suggest that miR-125a promotes chemo-resistance to gemcitabine in pancreatic cells through targeting A20, which may provide novel therapeutic targets or molecular biomarkers for cancer therapy and improve tumor diagnosis or predictions of therapeutic responses.